DNAX accessory molecule 1 (DNAM-1; CD226) is a costimulatory molecule belonging to the immunoglobulin superfamily. DNAM-1 is primarily expressed on NK and CD8 T cells, which has been shown to enhance the cytotoxic effector function of NK cells and T cells against tumor- and virus-infected cells. DNAM-1 is a member of the Ig superfamily, encoded by a gene on human chromosome 18q22.3, is expressed by human NK cells, T cells, a subset of B cells, monocytes and platelets. Interactions between DNAM-1 on NK cells and its ligands on tumour cells augments the NK cell–mediated cytotoxicity and cytokine production. CD155 and its related family member CD112, the known ligands for DNAM-1, broadly expressed on hematopoietic, epithelial, and endothelial cells. Moreover, it was shown that the interaction of DNAM-1 with CD112 and CD155 contributes to the NK-mediated lysis of both imDCs and mDCs. NK cells also express CD96, which shows only ∼20% homology to DNAM-1 but was also shown to recognize CD155 and promote NK cell adhesion and activation. Decreased NK cell activity has been observed in patients with PDAC, and pancreatic cancer patients have less CD226+ NK cells in the blood than do healthy controls. Dysregulation of DNAM-1 is associated with susceptibility to juvenile idiopathic arthritis, type 1 diabetes (T1D), lupus, and rheumatoid arthritis in patients.

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